Effect of ethanol on cholecystokinin-stimulated zymogen conversion in pancreatic acinar cells

Mark Katz, Robert Carangelo, Laurence J. Miller, Fred Gorelick

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

Exocrine pancreatic zymogens are proteolytically processed to active forms after they are secreted into the small intestine. However, intracellular conversion of zymogens to active forms can be stimulated by treating pancreatic acinar cells with high doses of cholecystokinin (0.1 μM) or carbamylcholine (0.1 mM). The high doses of cholecystokinin are unlikely to be achieved physiologically. The ability of ethanol to sensitize the acinar cell to zymogen conversion induced by cholecystokinin or carbamylcholine was examined. Ethanol (10-200 mM) had no effect alone or when combined with carbamylcholine. However, ethanol (25 mM) added with low-dose cholecystokinin (0.1 nM) generated zymogen conversion that was 1) sixfold higher than cholecystokinin alone and 2) equivalent to that generated by high-dose cholecystokinin (10 μM). The ability of ethanol to enhance cholecystokinin- induced zymogen conversion was dependent on the dose of ethanol and the duration of ethanol treatment. The cholecystokinin receptor antagonist, L- 364,718, blocked the conversion stimulated by the addition of ethanol with cholecystokinin. This effect of ethanol did not change the affinity or number of cholecystokinin receptors, suggesting an effect more distal in the stimulus-activation cascade. Those findings demonstrate that ethanol selectively sensitizes the pancreatic acinar cell to cholecystokinin- stimulated zymogen proteolysis.

Original languageEnglish (US)
Pages (from-to)G171-G175
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume270
Issue number1 33-1
StatePublished - Feb 26 1996

Keywords

  • alcohol
  • carboxy peptides
  • pancreatitis
  • proteolysis

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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